Toxicity

Most of the existing acute studies were conducted in rats, but mice and guinea pigs were also studied. No information was located regarding health effects in humans following acuteduration exposure to hexachlorobenzene by any route. The available animal data were sufficient to identify target organs of acute oral exposure. Extensive study of animals exposed by the oral route for acute durations has identified doses producing a wide range of health effects, including porphyria and other hepatic effects, renal tubular lesions, changes in thyroid and reproductive hormone levels, impaired male reproductive performance, developmental effects ranging from subtle neurobehavioral effects in neonates to fetotoxic and teratogenic effects, overt neurological effects, and lethality.

The World Health Organization has classified hexachlorobenzene as Class Ia extremely hazardous as it has caused a serious outbreak of porphyria in humans. Studies performed by the U.S. EPA placed hexachlorobenzene formulations in Acute Toxicity Rankings in a Category 3 and 4, Not Acutely Toxic to Slightly Toxic (Table below)

Study Type

Route

Species

Result

Units

LC50

Inhalation

Cat

1 600

mg/m3

LC50

Inhalation

Mouse

4 000

mg/m3

LC50

Inhalation

Rabbit

1 800

mg/m3

LC50

Inhalation

Rat

3 600

mg/m3

LC50

Oral

Cat

1 700

mg/kg

LC50

Oral

Mouse

4 000

mg/kg

LC50

Oral

Rabbit

2 600

mg/kg

LC50

Oral

Rat

10 000

mg/kg

Most of the existing subchronic toxicity studies were conducted in rats, but monkeys, mice, rabbits, dogs, and pigs were also studied. Extensive study of animals exposed by the oral route for intermediate durations has identified doses producing a broad spectrum of health effects, including porphyria and other hepatic effects, renal tubular lesions, pulmonary lesions, cardiac lesions, anemia and leukocytosis, osteosclerotic changes in bone, necrotic lesions in muscle, skin lesions, thymic atrophy, splenomegaly and altered spleen morphology, lymph node histopathology, altered immunoglobulin levels, suppression of immune function, changes in the thyroid, parathyroid, and adrenal glands and associated hormone levels, ovarian and testicular lesions, alterations in female menstrual cycling and reproductive hormone levels, reduced fertility, developmental effects ranging from subtle neurobehavioral effects in neonates to fetotoxic effects and pup death, overt neurological effects, and lethality. A few casecontrol studies have found evidence of developmental toxicity in newborn humans; no information was located regarding health effects in humans following subchronic exposure to hexachlorobenzene by any route.

There are data available on humans chronically exposed to hexachlorobenzene by the inhalation and oral routes, but no quantitative exposure information. The inhalation data are very limited, but tentatively found effects on the liver and immune system of exposed individuals. The oral data much more clearly identified the liver, skin, bone, thyroid, and central nervous system as target tissues for hexachlorobenzene in chronically exposed people. Based on very limited data, the original investigators of the Turkey epidemic estimated that the daily average oral dose was 0.050.2 g/day (0.72.9 mg/kg/day for a 70kg person). No information regarding chronic dermal exposure in humans was located. Chronic oral animal studies identified dose levels associated with systemic (cardiovascular, gastrointestinal, hematological, hepatic, renal, and dermal), immunological, overt neurological and developmental effects, as well as death. No chronic animal studies were located using inhalation or dermal exposure.